chr12-91000205-T-G

Variant names:

• chr12-91000205-T-G
• rs1920752
• NM_004950.5:c.165+2196A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004950.5(EPYC):​c.165+2196A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 151,962 control chromosomes in the GnomAD database, including 50,687 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (50687 hom., cov: 31)
• Consequence: EPYC NM_004950.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608
• Publications: 2 publications found

Genes affected

EPYC (HGNC:3053): (epiphycan) Dermatan sulfate proteoglycan 3 is a member of the small leucine-rich repeat proteoglycan family. This gene is composed of seven exons. It regulates fibrillogenesis by interacting with collagen fibrils and other extracellular matrix proteins. [provided by RefSeq, Jul 2008]

EPYC Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004950.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPYC	NM_004950.5	MANE Select	c.165+2196A>C		intron	N/A	NP_004941.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPYC	ENST00000261172.8	TSL:1 MANE Select	c.165+2196A>C		intron	N/A	ENSP00000261172.3
	EPYC	ENST00000551767.1	TSL:3	c.165+2196A>C		intron	N/A	ENSP00000448272.1
	EPYC	ENST00000550203.1	TSL:3	n.69+2196A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.815 AC: 123685 AN: 151842 Hom.: 50665 Cov.: 31

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.813

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.814 AC: 123753 AN: 151962 Hom.: 50687 Cov.: 31 AF XY: 0.815 AC XY: 60506 AN XY: 74248

African (AFR) AF: 0.720 AC: 29845 AN: 41430

American (AMR) AF: 0.797 AC: 12145 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2969 AN: 3464

East Asian (EAS) AF: 0.803 AC: 4141 AN: 5154

South Asian (SAS) AF: 0.748 AC: 3607 AN: 4824

European-Finnish (FIN) AF: 0.907 AC: 9625 AN: 10608

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.865 AC: 58784 AN: 67930

Other (OTH) AF: 0.810 AC: 1713 AN: 2114

Alfa AF: 0.810 Hom.: 2853

Bravo AF: 0.801

Asia WGS AF: 0.762 AC: 2644 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.66
DANN	Benign	0.74
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1920752; hg19: chr12-91393982;